We propose to continue examining genetic controls over the synthesis of enzymes related to the neural transmitters acetylcholine (ACh) and gamma-amino butyric acid (GABA). We propose to use the small soil nematode Caenorhabditis elegans because 1. It has a simple nervous system with reproducibly identifiable cells. 2. The physiological functions and transmitter-synthesizing capacities of many homologous cells are known in the larger nematode Ascaris lumbricoides. 3. Four mutations with severe effects on acetylcholine metabolism have already been identified. 4. C. elegans is genetically well suited for isolating new transmitter-related mutations. We propose to continue our analysis of apparent structural gene mutations affecting acetylcholinesterase and choline acetyl transferase, and we propose to use these in the coming year to isolate new structural gene alleles as well as regulatory gene mutations affecting these same enzymes. We also propose to begin in the coming year a search for mutations affecting the enzymes of GABA metabolism, namely glutamate decarboxylase, GABA-glutamate transaminase, and succinic semi-aldehyde dehydrogenase. In all cases, the available mutations will be used to determine the extent to which the function and formation of identified synaptic contacts depend on available transmitter levels.